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Genome-wide association study in patients with posterior urethral valves

Authors :
Loes F. M. van der Zanden
Carlo Maj
Oleg Borisov
Iris A. L. M. van Rooij
Josine S. L. T. Quaedackers
Martijn Steffens
Luca Schierbaum
Sophia Schneider
Lea Waffenschmidt
Lambertus A. L. M. Kiemeney
Liesbeth L. L. de Wall
Stefanie Heilmann
Aybike Hofmann
Jan Gehlen
Johannes Schumacher
Maria Szczepanska
Katarzyna Taranta-Janusz
Pawel Kroll
Grazyna Krzemien
Agnieszka Szmigielska
Michiel F. Schreuder
Stefanie Weber
Marcin Zaniew
Nel Roeleveld
Heiko Reutter
Wout F. J. Feitz
Alina C. Hilger
Source :
Frontiers in Pediatrics, Vol 10 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Congenital lower urinary tract obstructions (LUTO) are most often caused by posterior urethral valves (PUV), a male limited anatomical obstruction of the urethra affecting 1 in 4,000 male live births. Little is known about the genetic background of PUV. Here, we report the largest genome-wide association study (GWAS) for PUV in 4 cohorts of patients and controls. The final meta-analysis included 756 patients and 4,823 ethnicity matched controls and comprised 5,754,208 variants that were genotyped or imputed and passed quality control in all 4 cohorts. No genome-wide significant locus was identified, but 33 variants showed suggestive significance (P < 1 × 10−5). When considering only loci with multiple variants residing within < 10 kB of each other showing suggestive significance and with the same effect direction in all 4 cohorts, 3 loci comprising a total of 9 variants remained. These loci resided on chromosomes 13, 16, and 20. The present GWAS and meta-analysis is the largest genetic study on PUV performed to date. The fact that no genome-wide significant locus was identified, can be explained by lack of power or may indicate that common variants do not play a major role in the etiology of PUV. Nevertheless, future studies are warranted to replicate and validate the 3 loci that yielded suggestive associations.

Details

Language :
English
ISSN :
22962360
Volume :
10
Database :
Directory of Open Access Journals
Journal :
Frontiers in Pediatrics
Publication Type :
Academic Journal
Accession number :
edsdoj.2b86e5686ed44e1c9b5c76e66ebae75d
Document Type :
article
Full Text :
https://doi.org/10.3389/fped.2022.988374